Study Of Sunitinib In Combination With Cisplatin/Capecitabine Or Oxaliplatin/Capecitabine In Patients With Advanced Gastric Cancer

A Phase 1 Study Of Sunitinib Malate In Combination With Cisplatin/Capecitabine Or Oxaliplatin/Capecitabine In Patients With Advanced Gastric Cancer

The purpose of the study is to determine the safe and tolerable doses of sunitinib given together with either cisplatin and capecitabine or oxaliplatin and capecitabine in patients who have advanced gastric cancer who have not received prior chemotherapy for their advanced cancer

Study Overview

• Status: Completed
• Conditions: Stomach Neoplasms
• Intervention / Treatment: Drug: capecitabine; Drug: oxaliplatin; Drug: sunitinib malate; Drug: cisplatin

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Pfizer Investigational Site
  • Gyeonggi
    • Goyang, Gyeonggi, Korea, Republic of, 410-769
      • Pfizer Investigational Site
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• confirmed diagnosis of stomach cancer
• advanced stomach cancer of stage IV
• adequate blood chemistry, blood counts and kidney function
• willing to participate to study requirements and sign an informed consent document

Exclusion Criteria:

• prior chemotherapy for the stomach cancer in its advanced stage
• excessive toxicities related to prior therapies
• pregnant or breastfeeding patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: capecitabine; Capecitabine is given orally at 1000mg/m^2 twice a day for 14 days followed by 7 days of drug free period.; Drug: oxaliplatin; Oxaliplatin is given 110mg/m^2 through a vein on day 1 every 21 days. Each 21 day cycle is repeated until progression of disease or unacceptable toxicity is observed.; Drug: sunitinib malate; sunitinib is given orally 25mg/day for 14 days followed by 7 days of drug free period.; Other Names: Sutent
Experimental: B	Drug: capecitabine; Capecitabine is given orally at 1000mg/m^2 twice a day for 14 days followed by 7 days of drug free period.; Drug: sunitinib malate; sunitinib is given orally 25mg/day for 14 days followed by 7 days of drug free period.; Other Names: Sutent; Drug: cisplatin; Cisplatin is given 80mg/m^2 through a vein on day 1 every 21 days. Each 21 day cycle is repeated until progression of disease or unacceptable toxicity is observed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With First-cycle Dose Limiting Toxicities (DLTs)	Any DLT event in Cycle 1: Grade (GR) 3/4 nausea, vomiting, or diarrhea despite anti-emetics, anti-diarrheals; GR 3 nonhematological toxicity for greater than or equal to (≥)7 days (except alopecia, skin or hair discoloration, hyperamylasemia, or hyperlipasemia without other clinical evidence of pancreatitis and asymptomatic hyperuricemia); GR 4 nonhematological toxicity; GR 4 neutropenia ≥7 days or thrombocytopenia; GR ≥3 febrile neutropenia or neutropenic infection; GR 3 thrombocytopenia ≥7 days; any treatment-related toxicity having >3 consecutive CAP or SU missed doses per cycle; delayed toxicity recovery >14 days.	Baseline up to Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of SU, SU012662 (Metabolite of SU), and Total Drug (SU + SU012662)		Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose)
Cmax of CAP		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Cmax of 5'-Deoxy-5-fluorocytidine (Metabolite of CAP, 5'DFCR)		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Cmax of 5'-Deoxy-5-fluorouridine (Metabolite of CAP, 5'DFUR)		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Cmax of 5-fluorouracil (Metabolite of CAP, 5-FU)		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Minimum Observed Plasma Trough Concentration (Cmin) of SU, SU012662, and Total Drug (SU + SU012662)		Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose)
Cmin of CAP		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Cmin of 5'DFCR		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Cmin of 5'DFUR		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Cmin of 5-FU		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Time to Reach Maximum Observed Plasma Concentration (Tmax) for SU, SU012662, and Total Drug (SU + SU012662)		Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose)
Tmax for CAP		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Tmax for 5'DFCR		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Tmax for 5'DFUR		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Tmax for 5-FU		Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Terminal Elimination Half-Life (t1/2) for SU, SU012662, and Total Drug (SU + SU012662)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose)
t1/2 for CAP	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
t1/2 for 5'DFCR	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
t1/2 for 5'DFUR	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
t1/2 for 5-FU	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose); Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Area Under the Curve From Time 0 to 24 Hours Postdose (AUC [0-24]) for SU, SU012662, and Total Drug (SU + SU012662)	Area under the plasma concentration-time curve from time 0 to 24 hours postdose (0-24), also considered the AUC between doses at steady state.	Day 14 of Cycle 1 (predose and 2, 4, 6, 8, 10, and 24 hours postdose)
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]: CAP, 5'DFCR, 5'DFUR, and 5-FU	AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).	Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Area Under the Curve From Time Zero to 12 Hours [AUC (12)] for CAP, 5'DFCR, 5'DFUR, and 5-FU	AUC (12) = Area under the plasma concentration versus time curve from time zero (predose) to the extrapolated time 12 hours postdose. It is obtained from AUC (0 - last) plus AUC (last - 12)	Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose)
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for CAP	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours)
AUClast for 5'DFCR	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours)
AUClast for 5'DFUR	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours)
AUClast for 5-FU	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	Day 1 of Cycle 1 (0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours postdose) and Day 14 of Cycle 1 (predose and 0.25, 0.5, 1, 2, 3, 4, 8, and 10 hours)
Percentage of Participants With Objective Response	Percentage of participants with an objective response-based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as the disappearance of all target lesions. PR defined as ≥30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.	Baseline, Day 21 of every even-numbered cycle up to 15 months
Duration of Response (DR)	DR defined as time from start of first documented objective tumor response (CR or PR) to first documented objective tumor progression or death due to any cause, whichever occurs first.	Baseline up to Month 15
Progression-Free Survival (PFS)	PFS defined as time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.	Baseline up to Month 15

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Lee KW, Park SR, Oh DY, Park YI, Khosravan R, Lin X, Lee SY, Roh EJ, Valota O, Lechuga MJ, Bang YJ. Phase I study of sunitinib plus capecitabine/cisplatin or capecitabine/oxaliplatin in advanced gastric cancer. Invest New Drugs. 2013 Dec;31(6):1547-58. doi: 10.1007/s10637-013-0032-y. Epub 2013 Oct 4.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: November 6, 2007
• First Submitted That Met QC Criteria: November 6, 2007
• First Posted (Estimate): November 8, 2007

Study Record Updates

• Last Update Posted (Estimate): January 14, 2013
• Last Update Submitted That Met QC Criteria: January 7, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Capecitabine; Sunitinib; Oxaliplatin
• Other Study ID Numbers: A6181126